Our initial studies were intended to determine the effect of malignancy on human monocyte cytotoxicity to tumor cells in vitro. We observed that monocytes from untreated patients with lymphoma, breast cancer and colon carcinoma were able to interact with and kill tumor cells in a manner comparable to monocytes from normal healthy adult donors. In addition, sera from these cancer patients had no deleterious effect on the tumoricidal function of monocytes from normal donors. Thus, monocytes from cancer patients do not appear to be impaired in the functional capacity to bind and kill malignant tumor cells. To determine whether the tumoricidal function of human monocytes could be modulated, we have studied the effects of several biological response modifiers on monocyte cytotoxicity. Pretreatment of monocytes with interferon (IFN) or an IFN inducer elicited a significant increase in the capacity of these cells to kill malignant cells in vitro. All three types of human IFN, alpha, beta and gamma, were effective, including purified IFN-alpha from the cloned gene. The relationship of this activation of monocyte function and IFN therapy in cancer is being considered.